Sanford-Burnham Medical Research Institute (SBMRI) is an independent nonprofit research and graduate degree-granting institute located in La Jolla, CA, that conducts laboratory-based biomedical research funded primarily through NIH grants. The mission of the SBMRI Cancer Center is to be a national leader in the effort to overcome cancer as a cause of human suffering and death. Our vision is to make paradigm-shifting discoveries that will underlie novel therapeutic modalities by creating, translating, and disseminating exceptional cancer basic science. We will attain this by: 1. Conducting state-of-the-art, multidisciplinary basic research into the causes, prevention, and treatment of cancer. 2. Advancing our discoveries into early preclinical development for the benefit of cancer patients everywhere. 3. Educating and training the next generation of cancer scientists. The CCSG application details our plans for advancing our early translational cancer research capabilities that include basic cancer discovery (novel gene targets and mechanisms), an area of long-standing exceptional strength at SBMRI Cancer Center. Advancing our scientific discoveries will take place through several platforms, including small-molecule-based drug discovery, an area where we have significant technical capabilities and experience, and early preclinical therapeutic development, a growing strength. The Cancer Center is organized around three programs that encompass the cancer continuum: Tumor Initiation and Maintenance, Cell Death and Survival Networks, and Tumor Microenvironment and Metastasis, each with three sub-themes based on the hallmarks of cancer. We describe 9 Shared Resources and a new developing Shared Resource, Cancer Metabolism, that are critical for achieving the scientific goals of the Programs with which they are tightly interwoven. We describe the past use of CCSG Developmental funds for supporting the recruitment of new faculty, collaborative translational pilot projects driven by Center investigators, and therapeutic development pilot projects through a new STRIVE program. We also describe the San Diego National Cancer Institute Centers Council (C3), a new collaborative initiative between the 3 San Diego NCI-designated Cancer Centers, SBMRI, UCSD and the Salk Institute, leveraging the unique skills and resources of each Center for the treatment, and ultimate cure of cancer. The application highlights the progress made towards achieving our vision through multi-level strategic planning and evaluation, investments, recruitments, collaborations, organizational changes, and research accomplishments. Situated in San Diego, the fifth most populous county and the second largest life sciences cluster in the US, SBMRI Cancer Center is poised to achieve its vision by leveraging its scientific strengths through collaborations with academic and private sector investigators locally, nationally and internationally.